thromboplastin and Respiratory-Insufficiency

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human respiratory viral infection that has rapidly progressed into a pandemic, causing significant morbidity and mortality. Blood clotting disorders and acute respiratory failure have surfaced as the major complications among the severe cases of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection. Remarkably, more than 70% of deaths related to COVID-19 are attributed to clotting-associated complications such as pulmonary embolism, strokes and multi-organ failure. These vascular complications have been confirmed by autopsy. This study summarizes the current understanding and explains the possible mechanisms of the blood clotting disorder, emphasizing the role of (1) hypoxia-related activation of coagulation factors like tissue factor, a significant player in triggering coagulation cascade, (2) cytokine storm and activation of neutrophils and the release of neutrophil extracellular traps and (3) immobility and ICU related risk factors.

Topics: COVID-19; Cytokine Release Syndrome; Disseminated Intravascular Coagulation; Extracellular Traps; Gene Expression Regulation; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-6; Neutrophils; Pulmonary Embolism; Respiratory Insufficiency; SARS-CoV-2; Signal Transduction; Thromboplastin

Although enteral nutrition (EN) is provided to most mechanically ventilated patients, the effect of specific feeding strategies on circulating markers of coagulation and inflammation is unknown.. Markers of inflammation (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, interferon [IFN]-γ, IL-6, IL-8, IL-10, IL-12) and coagulation (tissue factor [TF], plasminogen activator inhibitor-1) were measured at baseline (n = 185) and 6 days (n = 103) in mechanically ventilated intensive care unit patients enrolled in a randomized controlled study of trophic vs full-energy feeds to test the hypothesis that trophic enteral feeds would be associated with decreases in markers of inflammation and coagulation compared to full-energy feeds.. There were no differences in any of the biomarkers measured at day 6 between patients who were randomized to receive trophic feeds compared to full-energy feeds. However, TF levels decreased modestly in patients from baseline to day 6 in the trophic feeding group (343.3 vs 247.8 pg/mL, P = .061) but increased slightly in the full-calorie group (314.3 vs 331.8 pg/mL). Lower levels of TF at day 6 were associated with a lower mortality, and patients who died had increasing TF levels between days 0 and 6 (median increase of 39.7) compared to decreasing TF levels in patients who lived (median decrease of 95.0, P = .033).. EN strategy in critically ill patients with acute respiratory failure does not significantly modify inflammation and coagulation by day 6, but trophic feeds may have some modest effects in attenuating inflammation and coagulation.

Topics: Adult; Aged; Biomarkers; Blood Coagulation; Critical Illness; Energy Intake; Enteral Nutrition; Female; Humans; Inflammation; Inflammation Mediators; Intensive Care Units; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Respiration; Respiration, Artificial; Respiratory Insufficiency; Thromboplastin

To investigate the role of endothelial cell mediators, E-selectin (ES), intercellular adhesion molecule-1 (ICAM-1), tissue factor (TF), and von Willebrand factor (vWF), in the early phase of severe acute pancreatitis (SAP) complicated with respiratory failure [pancreatitis-associated lung injury (PALI)].. This study included 30 patients with SAP and 39 patients with PALI. Blood samples were taken from SAP and PALI patients on presenting to the hospital (day 1), and days 2, 3, 5, and 10. The relationship between blood concentrations of the studied endothelial mediators and lung function tests was analyzed.. PALI patients had significantly higher ES, ICAM-1, TF, and vWF blood levels than those with SAP as early as at admission and throughout the period studied. We found the highest concentration of ES on the second day, ICAM-1 and TF at admission, and vWF level on the fifth day. There were adverse correlations between ES, ICAM-1, TF, vWF concentrations, and the index of oxygenation--PaO2/FiO2 ratio (Rs=-0.385, Rs=-0.523, Rs=-0.505, Rs=-0.408, P<0.001, respectively). The most accurate prediction of PALI was provided by ICAM-1 and TF levels on the day of admission [areas under curve (AUCs): ES, 0.704; ICAM-1, 0.787; TF, 0.757; and vWF, 0.686].. Endothelium-related mediators ES, ICAM-1, TF, and vWF appear to participate in pancreatitis-associated lung injury. In SAP, the measurement of endothelial mediator levels (especially ICAM-1 and TF) may be used as an early prognostic indicator that would predict the development of respiratory failure and to monitor the severity of lung dysfunction.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Area Under Curve; E-Selectin; Female; Humans; Intercellular Adhesion Molecule-1; Male; Middle Aged; Oxygen; Pancreatitis; Partial Pressure; Predictive Value of Tests; Prospective Studies; Respiratory Function Tests; Respiratory Insufficiency; ROC Curve; Thromboplastin; Time Factors; von Willebrand Factor; Young Adult

Pulmonary tumor thrombotic microangiopathy is an unusual malignancy-related respiratory complication characterized by multiple microthrombi and intimal myofibroblast proliferation. Its clinical manifestation is subacute respiratory failure with pulmonary hypertension. Herein is reported a case of pulmonary tumor thrombotic microangiopathy associated with gastric signet ring cell carcinoma. A 51-year-old woman with gastric cancer died of subacute respiratory failure. Autopsy showed gastric signet ring cell carcinoma with diffuse metastasis of pulmonary lymphatics and pleurae; every organ examined lacked a space-occupying tumor mass. Histologically, proliferated intimal myofibroblasts obliterated most of the pulmonary vascular lumen, and a few stenosed vascular lumina contained cancer cells. In addition, pulmonary vasculature associated with intimal proliferation contained microthrombi. Most cancer cells in the stomach and pulmonary lymphatics were typical signet ring cells, whereas those in vascular lesions were cells of poorly differentiated adenocarcinoma without mucous production. Consistent with a previous report, the latter expressed vascular endothelial growth factor (VEGF) and tissue factor (TF). The proliferated intimal myofibroblasts also expressed type 2A serotonin receptor (5-HT(2A)). These findings suggest that local expression of VEGF, TF, and 5-HT(2A) may be linked to the pathogenesis of this unusual pulmonary complication.

Topics: Carcinoma, Signet Ring Cell; Endothelium, Vascular; Fatal Outcome; Female; Humans; Hypertension, Pulmonary; Lung; Lung Neoplasms; Microcirculation; Middle Aged; Neoplastic Cells, Circulating; Receptor, Serotonin, 5-HT2A; Respiratory Insufficiency; Stomach Neoplasms; Thromboembolism; Thromboplastin; Vascular Endothelial Growth Factor A

Tissue factor expression in sepsis activates coagulation in the lung, which potentiates inflammation and leads to fibrin deposition. We hypothesized that blockade of factor X binding to the tissue factor-factor VIIa complex would prevent sepsis-induced damage to the lungs and other organs. Acute lung injury was produced in 15 adult baboons primed with killed Escherichia coli [1 x 10(9) colony-forming units (CFU)/kg], and then 12 h later, they were given 1 x 10(10) CFU/kg live E. coli by infusion. Two hours after live E. coli, animals received antibiotics with or without monoclonal antibody to tissue factor intravenously to block tissue factor-factor X binding. The animals were monitored physiologically for 34 h before being killed and their tissue harvested. The antibody treatment attenuated abnormalities in gas exchange and lung compliance, preserved renal function, and prevented tissue neutrophil influx and bowel edema relative to antibiotics alone (all P < 0.05). It also attenuated fibrinogen depletion (P < 0.01) and decreased proinflammatory cytokines, e.g., IL-6 and -8 (P < 0.01), in systemic and alveolar compartments. Similar protective effects of the antibody on IL-6 and -8 expression and permeability were found in lipopolysaccharide-stimulated endothelial cells. Blockade of factor X binding to the tissue factor-factor VIIa complex attenuates lung and organ injuries in established E. coli sepsis by attenuating the neutrophilic response and inflammatory pathways.

Topics: Animals; Antibodies, Monoclonal; Blood Circulation; Capillary Permeability; Cells, Cultured; Cytokines; Endothelial Cells; Escherichia coli Infections; Factor X; Humans; Immunoglobulin Fab Fragments; Inflammation Mediators; Lipopolysaccharides; Male; Papio; Renal Insufficiency; Respiratory Insufficiency; Thromboplastin

Surfactant abnormalities have been implicated in the development of the acute respiratory distress syndrome in adults. Experimental studies show that surfactant inhibition by protein-leak into the alveolar space is of major importance under these circumstances. Fibrin(ogen)-surfactant-interaction appears to contribute to disturbances of surfactant function with subsequent alveolar instability and ventilation-perfusion-mismatch. In a prospective study in severely injured patients, the surfactant in serially obtained bronchoalveolar lavage fluids was investigated. An early leakage of plasma proteins into the alveolar space was noted in those patients, who developed severe ARDS. Moreover, deterioration of surfactant function was markedly more pronounced in those patients than in trauma victims who developed only mild pulmonary dysfunction. In addition to the protein-leakage, a progressive decrease of the surfactant-specific dipalmitoyl-phosphatidylcholine was noted, significantly correlated with the deterioration of surfactant function and the severity of respiratory failure. In conclusion, experimental and clinical studies show surfactant abnormalities in the adult respiratory distress syndrome. Plasma protein-leakage and progressive alteration of alveolar type II surfactant secretion appear to be of major importance.

Topics: Adult; Bronchoalveolar Lavage Fluid; Factor VII; Humans; Lung Compliance; Multiple Trauma; Pulmonary Surfactants; Respiratory Distress Syndrome; Respiratory Insufficiency; Severity of Illness Index; Thromboplastin

The possible association between acute respiratory failure and disseminated intravascular coagulation was examined in eight patients with severe acute respiratory failure--a condition characterized by tachypnea, right to left intrapulmonary shunting of blood greater than 30 per cent of cardiac output, increased pulmonary artery pressure with low or normal pulmonary artery wedge pressure and roentgenologic interstitial pulmonary edema. Treatment consisted of mechanical ventilation with positive end expiratory pressure sufficient to minimize intrapulmonary shunting. There was no abnormality in platelet concentration fibrin split product concentration, fibrinogen concentration, prothrombin time or activated partial thromboplastin time during the period of most severe respiratory failure in any patient. However, mean platelet concentration fell to 90,000+/-9,000 per cubic millimeter, less than 0.001, and mean fibrin split product levels rose to 60+/-10 micrograms per milliliter, p less than 0.05, the fourth day after the onset of acute respiratory failure. No significant change occurred in other coagulation parameters. Disseminated intravascular coagulation developed in none of the patients nor was there any correlation between coagulation abnormalities and severity of acute respiratory failure that would suggest a cause and effect relationship.

Topics: Acute Disease; Adult; Blood Cell Count; Blood Platelets; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Male; Middle Aged; Oxygen; Positive-Pressure Respiration; Prothrombin Time; Respiratory Insufficiency; Thromboplastin